コンテンツにスキップ

TNF受容体1型

出典: フリー百科事典『ウィキペディア(Wikipedia)』
TNFRSF1Aから転送)
TNFRSF1A
PDBに登録されている構造
PDBオルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧

1EXT, 1FT4, 1ICH, 1NCF, 1TNR

識別子
記号TNFRSF1A, CD120a, FPF, MS5, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR1, TNFR1-d2, TNFR55, TNFR60, p55, p55-R, p60, tumor necrosis factor receptor superfamily member 1A, TNF receptor superfamily member 1A
外部IDOMIM: 191190 MGI: 1314884 HomoloGene: 828 GeneCards: TNFRSF1A
遺伝子の位置 (ヒト)
12番染色体 (ヒト)
染色体12番染色体 (ヒト)[1]
12番染色体 (ヒト)
TNFRSF1A遺伝子の位置
TNFRSF1A遺伝子の位置
バンドデータ無し開始点6,328,757 bp[1]
終点6,342,114 bp[1]
遺伝子の位置 (マウス)
6番染色体 (マウス)
染色体6番染色体 (マウス)[2]
6番染色体 (マウス)
TNFRSF1A遺伝子の位置
TNFRSF1A遺伝子の位置
バンドデータ無し開始点125,326,325 bp[2]
終点125,339,447 bp[2]
RNA発現パターン
さらなる参照発現データ
遺伝子オントロジー
分子機能 血漿タンパク結合
tumor necrosis factor-activated receptor activity
tumor necrosis factor binding
identical protein binding
細胞の構成要素 integral component of membrane
ゴルジ体

ゴルジ膜
receptor complex
細胞膜
integral component of plasma membrane
細胞外領域
cell surface
ミトコンドリア
脂質ラフト
細胞外空間
tumor necrosis factor receptor superfamily complex
生物学的プロセス regulation of apoptotic process
prostaglandin metabolic process
防衛反応
positive regulation of ceramide biosynthetic process
positive regulation of inflammatory response
regulation of tumor necrosis factor-mediated signaling pathway
tumor necrosis factor-mediated signaling pathway
リポ多糖への反応
cellular response to mechanical stimulus
death-inducing signaling complex assembly
regulation of cell population proliferation
defense response to bacterium
免疫応答
intrinsic apoptotic signaling pathway in response to DNA damage
positive regulation of I-kappaB kinase/NF-kappaB signaling
viral process
I-kappaB kinase/NF-kappaB signaling
negative regulation of inflammatory response
regulation of establishment of endothelial barrier
extrinsic apoptotic signaling pathway via death domain receptors
positive regulation of transcription by RNA polymerase II
シグナル伝達
アポトーシス
炎症反応
細胞表面受容体シグナル伝達経路
positive regulation of tyrosine phosphorylation of STAT protein
protein localization to plasma membrane
サイトカイン媒介シグナル伝達経路
大動脈弁発生
肺動脈弁発生
negative regulation of extracellular matrix constituent secretion
negative regulation of cardiac muscle hypertrophy
positive regulation of apoptotic process involved in morphogenesis
出典:Amigo / QuickGO
オルソログ
ヒトマウス
Entrez
Ensembl
UniProt
RefSeq
(mRNA)

NM_001065
NM_001346091
NM_001346092

NM_011609

RefSeq
(タンパク質)

NP_001056
NP_001333020
NP_001333021

NP_035739

場所
(UCSC)
Chr 12: 6.33 – 6.34 MbChr 12: 125.33 – 125.34 Mb
PubMed検索[3][4]
ウィキデータ
閲覧/編集 ヒト閲覧/編集 マウス

TNF受容体1型(1型TNF受容体、tumor necrosis factor receptor 1、TNFR1)、TNFRSF1A(tumor necrosis factor receptor superfamily, member 1A)またはCD120aTNF-αを結合する膜受容体であり、普遍的に発現している[5][6][7]

機能

[編集]

TNFRSF1A遺伝子にコードされるTNFR1は、TNFR2英語版などとともにTNF受容体スーパーファミリー英語版を構成する。このタンパク質はTNF-αに対する主要な受容体の1つであり、転写因子NF-κBの活性化、アポトーシスの媒介、炎症の調節といった機能を果たす。抗アポトーシスタンパク質BAG4英語版アダプタータンパク質TRADD英語版TRAF2英語版がこの受容体と相互作用することが示されており、これらは受容体によって媒介されるシグナル伝達を調節する役割を果たしている[8]

臨床的意義

[編集]

この受容体の細胞外ドメイン領域に生じた生殖細胞系列変異英語版は、TNF受容体関連周期性症候群英語版(TRAPS)と呼ばれる遺伝疾患との関連が示されている[9]。この疾患の機序には受容体のクリアランスの機能不全が関係していると考えられている。

TNFRSF1A遺伝子の変異は、多発性硬化症のリスクの増大と関連している[10]

統合失調症双極性障害の患者では血清中の可溶性TNFR1濃度が上昇しており[11]、高値はより重篤な精神症状と関連している[12]。また、血清中の高濃度は認知機能障害や認知症とも関連している[13][14]

相互作用

[編集]

TNFRSF1Aは次に挙げる因子と相互作用することが示されている。

出典

[編集]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000067182 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030341 - Ensembl, May 2017
  3. ^ Human PubMed Reference:
  4. ^ Mouse PubMed Reference:
  5. ^ “Chromosomal location of the human tumor necrosis factor receptor genes”. Cytogenet Cell Genet 57 (2–3): 117–8. (November 1991). doi:10.1159/000133127. PMID 1655358. 
  6. ^ “Molecular cloning and expression of a receptor for human tumor necrosis factor”. Cell 61 (2): 361–70. (June 1990). doi:10.1016/0092-8674(90)90816-W. PMID 2158863. http://www.escholarship.org/uc/item/39j2j0h2. 
  7. ^ Offermanns, Stefan; Rosenthal, Walter (2008). Encyclopedia of Molecular Pharmacology, Vol. 1 (2nd ed.). Heidelberg, Germany: Springer. p. 1248. ISBN 9783540389163. https://books.google.com/books?id=iwwo5gx8aX8C 
  8. ^ Entrez Gene: TNFRSF1A tumor necrosis factor receptor superfamily, member 1A”. 2007年11月2日閲覧。
  9. ^ “Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis”. Nat Rev Neurol 5 (10): 528–9. (October 2009). doi:10.1038/nrneurol.2009.154. PMID 19794511. 
  10. ^ International Multiple Sclerosis Genetics Consortium (2011). “The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study”. PLOS ONE 6 (4): e18813. Bibcode2011PLoSO...618813.. doi:10.1371/journal.pone.0018813. PMC 3084233. PMID 21552549. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084233/. 
  11. ^ “Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor”. Bipolar Disord 11 (7): 726–34. (November 2009). doi:10.1111/j.1399-5618.2009.00757.x. hdl:10852/34620. PMID 19839997. 
  12. ^ “Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder”. Schizophr. Res. 145 (1–3): 36–42. (April 2013). doi:10.1016/j.schres.2012.12.023. PMID 23403415. 
  13. ^ “Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment”. Neurobiol. Aging 31 (11): 1877–84. (November 2010). doi:10.1016/j.neurobiolaging.2008.10.012. PMID 19070941. 
  14. ^ “Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease”. J. Alzheimers Dis. 22 (4): 1305–11. (2010). doi:10.3233/JAD-2010-100921. PMID 20930310. 
  15. ^ a b “Prevention of constitutive TNF receptor 1 signaling by silencer of death domains”. Science 283 (5401): 543–6. (1999). Bibcode1999Sci...283..543J. doi:10.1126/science.283.5401.543. PMID 9915703. 
  16. ^ “Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain”. Mol. Cell. Biol. 22 (8): 2536–43. (2002). doi:10.1128/MCB.22.8.2536-2543.2002. PMC 133739. PMID 11909948. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133739/. 
  17. ^ a b “Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy”. J. Biol. Chem. 280 (12): 11641–7. (2005). doi:10.1074/jbc.M411781200. PMID 15659383. 
  18. ^ “Fas-associated death domain protein interleukin-1beta-converting enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55-mediated death signaling”. J. Biol. Chem. 272 (10): 6578–83. (1997). doi:10.1074/jbc.272.10.6578. PMID 9045686. 
  19. ^ a b c “TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways”. Cell 84 (2): 299–308. (1996). doi:10.1016/S0092-8674(00)80984-8. PMID 8565075. 
  20. ^ “Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation”. Immunity 12 (3): 301–11. (2000). doi:10.1016/S1074-7613(00)80183-1. PMID 10755617. 
  21. ^ “Activation of the NF-kappaB pathway by caspase 8 and its homologs”. Oncogene 19 (39): 4451–60. (2000). doi:10.1038/sj.onc.1203812. PMID 11002417. 
  22. ^ a b “Induction of Jak/STAT signaling by activation of the type 1 TNF receptor”. J. Immunol. 160 (6): 2742–50. (1998). doi:10.4049/jimmunol.160.6.2742. PMID 9510175. 
  23. ^ “Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells”. Cell Growth Differ. 13 (1): 13–8. (2002). PMID 11801527. 
  24. ^ “A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase”. J. Biol. Chem. 272 (9): 5861–70. (1997). doi:10.1074/jbc.272.9.5861. PMID 9038203. 
  25. ^ “A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its 'death domain'”. FEBS Lett. 367 (1): 39–44. (1995). doi:10.1016/0014-5793(95)00534-G. PMID 7601280. 
  26. ^ “Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease”. J. Immunol. 158 (9): 4252–9. (1997). doi:10.4049/jimmunol.158.9.4252. PMID 9126987. 
  27. ^ a b c “TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex”. Immunity 4 (4): 387–96. (1996). doi:10.1016/S1074-7613(00)80252-6. PMID 8612133. 
  28. ^ “Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP”. Oncogene 19 (39): 4491–9. (2000). doi:10.1038/sj.onc.1203796. PMID 11002422. 
  29. ^ “RAIDD is a new 'death' adaptor molecule”. Nature 385 (6611): 86–9. (1997). Bibcode1997Natur.385...86D. doi:10.1038/385086a0. hdl:2027.42/62739. PMID 8985253. https://deepblue.lib.umich.edu/bitstream/2027.42/62739/1/385086a0.pdf. 
  30. ^ a b “Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)”. Biochem. J. 417 (1): 149–60. (2009). doi:10.1042/BJ20081885. PMID 18939944. 
  31. ^ “Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies”. Cell 134 (4): 668–78. (2008). doi:10.1016/j.cell.2008.07.039. PMID 18724939. 
  32. ^ “c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation”. J. Biol. Chem. 283 (36): 24295–9. (2008). doi:10.1074/jbc.C800128200. PMC 3259840. PMID 18621737. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259840/. 
  33. ^ “The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis”. J. Biol. Chem. 274 (15): 10145–53. (1999). doi:10.1074/jbc.274.15.10145. PMID 10187798. 
  34. ^ “Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin”. J. Immunol. 157 (10): 4277–81. (1996). doi:10.4049/jimmunol.157.10.4277. PMID 8906799. 
  35. ^ a b “The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex”. Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13973–8. (1996). Bibcode1996PNAS...9313973S. doi:10.1073/pnas.93.24.13973. PMC 19479. PMID 8943045. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC19479/. 
  36. ^ “Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling”. J. Biol. Chem. 274 (15): 10203–12. (1999). doi:10.1074/jbc.274.15.10203. PMID 10187805. 
  37. ^ “The receptor for the cytotoxic ligand TRAIL”. Science 276 (5309): 111–3. (1997). doi:10.1126/science.276.5309.111. PMID 9082980. 
  38. ^ “TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates activation of the transcription factor NF-kappaB”. Mol. Cell. Biol. 23 (22): 8334–44. (2003). doi:10.1128/MCB.23.22.8334-8344.2003. PMC 262424. PMID 14585990. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC262424/. 
  39. ^ “A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway”. Nat. Cell Biol. 6 (2): 97–105. (2004). doi:10.1038/ncb1086. PMID 14743216. 
  40. ^ “The TNF receptor 1: a split personality complex”. Cell 114 (2): 148–50. (2003). doi:10.1016/s0092-8674(03)00561-0. PMID 12887914. 
  41. ^ “hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity”. FEBS Lett. 425 (3): 431–5. (1998). doi:10.1016/S0014-5793(98)00287-7. PMID 9563508. 

関連文献

[編集]

関連項目

[編集]

外部リンク

[編集]